Determining the distribution of light absorbing substances which are located inside an opaque, light-scattering medium that hides the substances from view can be difficult. For example, forming an image of objects inside luggage presented at an airport checkpoint can require the use of x-rays, which may be harmful to those nearby, fog photographic film, and fail to detect certain plastic weaponry or explosives. Similarly, the detection of tumors inside the human body is difficult, and limited by the need to use x-rays or cumbersome magnetic imaging techniques, by the inability to image some types of tumors, and by cost. Lastly, identification of the amount of oxygen in blood deep inside the human body is of central importance in the medical management of many patients. For example, adults suffering heart attacks, children with severe asthma, and prematurely born babies, all need close monitoring of the amount of oxygen in their blood, and this can be determined in superficial tissues using photodetectors, but this method does not yield spatial information, leaving deep tissues, such as the heart itself or the fetus in the womb beyond the range of measurement. Currently available methods to image substances deep inside a light scattering body are hampered by physical limitations inherent in those methods. For example, the use of x-rays carries health risks, and does not image all substances. The use of sound waves, such as ultrasound, is limited by an inability to measure through air/fluid interfaces, and the images are not clear. Magnetic Resonance Imaging (MRI) is limited by the need for large, expensive, magnetically-shielded facilities, and is not appropriate for many situations.
Several techniques exist in the art which use light to measure substances in a scattering medium, but all contain significant drawbacks that prevent or hamper their usage as spatial imaging modalities. For example, reflectance pulse oximetry, taught by Taylor et al. (U.S. Pat. No. 4,859,057) and Sawa (U.S. Pat. No. 4,305,398), uses light reflected back from the skin or eye to measure the saturation of blood with oxygen. However, these measurements are only skin deep. Reflection oximetry does not reveal the distribution in space of this blood, only information about blood in the superficial tissues. Internal organs remain out of range because pulse oximetry devices do not work well when their light is directed deep into a body, for reasons due to the physics of the measurement, to be outlined below. Thus, despite recent improvements, there is currently no easy way to measure, for example, the quantity of oxygen a fetus is receiving while in its mother's womb. This lack of an adequate method to test fetal saturation contributes to unnecessary emergency surgical deliveries (Shy et. al., 1990), as well produces babies with cerebral palsy who went without adequate oxygen, but in whom this low oxygen level was not detected due to the lack of a simple, non-invasive method of checking fetal oxygen. Another example of the need for improvement in measurement is with newborns babies, who often undergo painful blood tests because there is no in vivo method at this time that quantitatively measures jaundice, an excess of light absorbing substance called bilirubin. A final example is the adult who needs x-rays to determine if a bone is broken, whereby the lack of a simple optical method necessitates the use of x-irradiation.
The limitations in current methods of optical spectroscopy, such as pulse oximetry and other methods of spectroscopy, are due to physical laws governing the measurements themselves, and these inherent limitations will become self evident upon close study of the mathematical relationship called Beer's Law, EQU A=.epsilon.CL, (1)
where absorbance of light (A) equals a known constant (.epsilon.) times the concentration of measured substance (C) times the path length of light through the tissue (L). The foundation for nearly all optical spectrophotometry, and of much of the spectrophotometry using other types of radiation in the art, whether specified outright or empirically derived, is Beer's Law rearranged to solve for concentration, as: EQU C=A/.epsilon.L. (2)
One problem encountered in implementing Beer's Law is that the path taken by photons of light as they travel through a light scattering medium is different for each photon. The same is true for other types of radiation, but light alone will be considered here for simplicity. Some photons travel straight through the medium, thus taking the shortest possible path, while others meander through the medium, thus taking a much longer path and taking much longer to pass through the medium. As a whole, the paths taken by a single large group of photons passing through the medium at the same time are multiple, and the paths are tortuous and irregular, so that a single exact path length L does not exist. Thus, when attempts to solve Beer's Law are made, there is no true L value that can be used. The fact that light has scattered prevents solution to Beer's Law, in all but specialized cases. In fact, Benaron (1991) was the first to show that even the range of path length L was so variable, even for common tissues such as brain, that path lengths must be measured in order to achieve an accurate estimate of absorption.
Jobsis (U.S. Pat. No. 4,805,623) was the first to attempt to address this problem. His device estimates a path length in a tissue with a known thickness and concentration of light absorbing substance, and then using the relative absorbance of that reference compared to a tissue under study, attempts to correct for uncertainties in path length. There are five major limitations inherent in Jobsis' approach, outlined in Benaron (pending U.S. Pat. No. 07/612,808). Chance (U.S. Pat. No. 4,972,331) introduces a modulated light source in order to determine a median time of travel, but this still does not yield spatial information, as the effect of the individual path lengths are blurred by an averaging process. The net result of this averaging process is that, at best, only a median time of travel may be deduced. Further, the intensity of the returning light is not contemporaneously measured, thus precluding the performance of certain analyses.
Benaron (pending U.S. Pat. No. 07/499,084) was the first to introduce true spatial resolution, teaching a pulsed light source that allows identification of a feature of the differing path lengths. When the continuous light used by others is turned off, and a pulsed, non-continuous light source is substituted, all photons entering the medium enter at approximately the same time. As the light source becomes dark after the pulse is produced, timing the exit of photons from the substances gives a clue as to the paths they have traveled. Light that travels the shortest distance through the medium now exits first and can be detected early, whereas light that travels the longest distance through the medium exits last and is detected later. In his patents pending, Benaron teaches how to measure a feature of the detected light signal (such as the brightest time point), which provided some of the information needed to correct Beer's Law for path length. For example, measuring the brightest point, allowed for a calculation of the modal path traveled by photons returning at that point in time. As the speed of light in tissues is relatively constant, all photons returning at that particular time have traveled about the same distance, assuming that they all were emitted at the same moment. This allowed determination of absorbance at one particular path length, but discards the range and other features of the distribution of paths taken.
Benaron substantially improved the power of his initial pulsed, noncontinuous light approach by analyzing the full spectrum of path lengths traveled (U.S. Pat. No. 07/612,808). Using a mathematical deconvolution algorithm, different characteristics of the medium and of the absorbing and scattering substances may be determined using TOFA (time of flight and absorbance) data from one or more points. This allowed determination of a multi-dimensional saturation image yielding absorbance at different depths in the tissue, or even three-dimensional absorbance distribution images. While the approach is effective, Singer et al., (1990) and Schlereth showed that production of an image required significant computer processing.
What is currently needed, and not available in the art, is a device capable of rapidly imaging a function of the absorbance and scattering of light traveling through light scattering tissues, one which does not require massive processing in order to produce an image, that will give real-time image information, and avoid the problems associated with computation-intensive path-length calculations.